Dengue Hemorrhage Fever 2

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DENGUE HEMORRHAGIC FEVER

Dr. CHOEUNG Chea

MD, MMed (Paediatrics)

Diseases in Childhood

Updated : April 2008

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TRANSMISSION OF DENGUE VIRUS• Dengue virus cMlgeTAmnusStamryHkarxaMebs;

infected Aedes aegypti. • Virus

eFVIdMeNIrkñúgcrnþQaménmnusSEdlva)anxaM eFVIeLIgkñúgkMLúgeBl EdlGñkCMgWmanRKunekþA.

• Uninfected mosquitoes Gacqøg virus

RbsinebIva)anxaMmnusSEdlkMBugenAkñúgtMNak;kal viremic

• Virus

bnÞab;mkk¾eFVIkarvivtþenAkñúgxøÜnrbs;musxøakñúgryHeBl 8-10éf¶ munnwgvaGaccMlgeTAmnusSepSgeTót kñúgkMLúgeBlbWtQam rweBlsuwcMNIGahar.

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THE VIRUS• Dengue virus sßitenAkñúg family Flaviridae.

• Dengue virus man 4 serotypes (DEN-1, DEN-2, DEN-3, DEN-4)

EdleKGacEbgEckva)anedaysar serological methods.

• .kalNamnusSqøgvIrusén serotype NamYy vanwgbegáIteGayman immunity

mYyCIvitRbqaMgnwg reinfection

edaysarvirusén serotype RbePTenaH b:uEnþvabegáIteGayman immunity temporary and

partial RbqaMgeTAnwgvIrusén serotypes

RbePTepSg²eTót .

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THE HOST

• .kñúgcMeNam serotypes TaMg4 énvIrusénCMgWRKunQam vIrusén serotypes NamYyk¾edayGacbgáeGayman DF and DHF )anEdr .

• Dengue shock syndrome (DSS) ekIteLIgenAelI– .buKþlEdlFøab;qøgCMgWRKunQamBImunmk (Previous dengue infection)

– .enAelITarkenAeBlEdlRbBn½ækarBarCMgWRKunQamrbs;mþay enAelITarkmankarfycuH (Infants with waning levels of maternal dengue antibody)

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THE HOST

• Incubation manryHeBl 3-14 éf¶• Acute phase of infection: 5-7 éf¶• Followed by an immune respond

• Infection elIkTImYybegáIteGayman immunity

mYyCIvitRbqaMgnwg reinfection

edaysarvirusén serotype RbePTenaH b:uEnþvabegáIteGayman immunity temporary and

partial RbqaMgeTAnwgvIrusén serotypes 3

RbePTepSgeTót . • Infections elIkTI2 rW bnÞab;mkeTót

GacekItmanenAmYyryHeBl xøIeRkaymk .

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-Fever

-Flushed face

-Headache

-Retro-orbital pain

-Myalgia

-Arthralgia

-Rash

-Haemorrhagic

manifestation

-Leucopenia

Thrombocytopenia*

Hepatomegaly

capillary

permeability

Serous

effusion

(pleural, ascite)

Hypoprotidemia

Hypovolemia

(haemoconcentration)Shock

DIC

Intestinal

haemorrhage

Acidosis

Anoxia

Dead

DFDHF

DSS

*Trombocytopenia is not constant in DF

DENGUE PATHOGENESIS

Ag-Ab-complement complex

Primary Dengue infection

Secondary dengue infection

Neutralizing Ab for the same serotype dengue virus

Non-neutralizing Abs → need to enhancing Ab for new infected dengue serotype

Ag – Ab complex

Chemical substances released: C3a, C5a, IL-1, IL-6, TNF-α,

Histamine Increased vascular permeability

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Central Peripheric

Bone marrow suppression

Utilization-Excessive used for platelet aggravation-Consumptive coagulopathy

Platelet destruction

MECANISM OF THROMBOCYTOPENIA

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Proposed Hypothesis of Liver Damage

• Dysregulation of host immune response against virus

• Direct viral effect

Manifestation of dengue virus infection

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Asymptomatic

Symptomatic

Undifferentiate fever

Dengue fever (DF)

Dengue haemorrhagic

fever (DHF)

Classical DF

DF with unusual haemorrhage

No shock (DHF grade I and II)

With shock (DHF grade III and IV)

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DIAGNOSIS OF THE DENGUE INFECTION

Febrile phase Afebrile phase

DF

Acute and very high fever + 2 or more of following signs: Flushed face and/or conjunctival injection Headache Retro-orbital pain Cutaneous rash Haemorrhagic manifestation (petechiae, Tourniquet test+) Lab: Leucopenia Ht: normal

minman aggravation énCMgWeT (xusBI DHF), fÞúyeTAvij sPaBrbs;GñkCMgW mankarRbesIreLIg Lab: Ht: always normal Platelet: normal or

Symptoms and Laboratory

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DIAGNOSIS OF THE DENGUE INFECTION

Febrile phase Afebrile phase

DHF

Above DF signs + always very sensitive hepatomegaly (abdominal pain) Lab: Ht: still normal Platelets: still normal

The child status deteriorates: somnolence important asthenia abdominal pain

hemodynamic status ± compensated No signs of shock Lab: Ht: 20% of normal value Platelets: 100.000/mm3

Symptoms and Laboratory

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DIAGNOSIS OF THE DENGUE INFECTION

Febrile phase Afebrile phase

DSS

Same symptoms as DF/DHF Lab: Ht: still normal Platelets: still normal

Same symptoms as DHF + signs of circulatory failure with shock Lab: Ht: 20% of normal value (except digestive haemorrhage) Platelets: 100.000/mm3

Symptoms and Laboratory

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Grading the severity of dengue infectionType Grade Symptoms Laboratory

DF DHF

I

II

Fever with 2 or more of the following signs: flushed face, headache, retro-orbital pain, myalgia, arthralgia, rash, haemorrhagic signs Above signs plus: positive tourniquet test and/or bruising (ecchymosis) Above signs plus spontaneous bleeding or haemorrhage

-Leucopenia - +/- Thrombocytopenia -Normal Ht -Thrombocytopenia 100.000/mm3 - Ht 20% of normal value -Thrombocytopenia 100.000/mm3 - Ht 20% of normal value

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Grading the severity of dengue infection

Type Grade Symptoms Laboratory

DSS

III

IV

Above signs plus circulatory failure (weak and rapid pulse, narrow BP, hypotension, cold and clammy skin, restlessness Pronfound shock with undertectable pulse and/or BP

-Thrombocytopenia 100.000/mm3 - Ht 20% of normal value (except digestive haemorrhage) -Thrombocytopenia 100.000/mm3 - Ht 20% of normal value (except digestive haemorrhage)

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Tourniquet Test• Raise the blood pressure to mid

way between systolic and diastolic pressure for 5 minutes.

• Release the pressure and wait for 1 minute before reading the result.

• Positive test is considered when there is 10 petechia per square inches or 2.5 cm square cm

2.5 cm

2.5 cm

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Baseline Value for Ht

• Age 2 years = 30-35%

• Age > 2-10 years = 35-40%

• Age > 10 years = 40-45%

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Laboratory Tests for Dengue Infection

• Uncomplicated DHF case: Ht & Platelet count

• Complicated DHF case:– Blood grouping– Blood sugar– Blood electrolyte– Liver function test– Renal function test – Blood gas– Coagulogram (PTT, PT, TT)

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Confirmed Laboratory Test for Dengue Infection

• Early test:– 1. Viral isolation– 2. Polymerase Chain Reaction (PCR)– 3. Antigen detection infixed tissues

• Late test:– Serology test- Antibody detection: detectable

around or after the time of defervescence (usually day 5-7 of illness)

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Differential Diagnosis• .kRBa©il: RKunekþAxøaMg 39-

40oC with oculo-nasal and bronchitic catarrh. Rash, specific to the disease on the 4th-5th day and persistent fever during the rash.

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Differential Diagnosis• Rubella (German measles):

RKunekþAmFümkñúgkMLúgeBl 3-4 éf¶ rYcbnþeday rash, which characterized the disease. Retro-cervical and occipital lymphadenopahties are common.

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Differential Diagnosis• Typhoid fever: fever progressively increasing up

to 39-40oC and persistent after the 7th day, saburral tongue and rumbling of the right iliac fossa.

• Malaria: fever with thrombocytopenia often associated. History of travel or live in a malaria endemic zone. The fever persists over 7 days.

• Meningococcal meningitis: the shock with thrombocytopenia, caused by the meningococcemia before the appearance of a necrotic purpura, can simulate DSS.

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MENAGEMENT OF DF

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MENAGEMENT OF DF• Febrile phase (2-7 days):

– .eGayGñkCMgWsMrakeGay)aneRcIn ,Oral rehydration

– . RbsinebIkMedA >38oC RtUveGay Paracetamol

10mg/kg/dose, kMueGayelIsBI 4dgkñúgmYyéf¶

– .minRtUveGay ASPIRIN eT– .RtYtBinitü pla/Ht erógral;éf¶;cab;éf¶TI 3 eTA

• Afebrile phase (2-3 days):

– . eGayGñkCMgWsMrakeGay)aneRcIn– . RtYtBinitü Pla/Ht 2 dgkñúg1éf¶kñúgryHeBl

24-48h– Oral fluid therapy

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MENAGEMENT OF DF

• Convalescence phase (7-10 days):

– .KµandMbUnµanGVIBiesseT (No special advice)

– .kumarGacjaMcMNIGaharFmµta (Normal diet without any restriction)

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MENAGEMENT OF DHF

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MANAGEMENT OF DHF

• The manifestations and management of DHF during the febrile phase are the same as DF.

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MENAGEMENT OF DHFGRADE I & II

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Type of IV fluids• Crystalloid solutions

- 5%D/NSS- 5%D/N/2* (only for < 1 year of age)- 5%DLR- 5%DAR

• Colloid solutions - 10% Dextran 40- 10% Haes-Sterile

D= Dextrose, NSS= Normal Saline Solution, AR= Acetate Ringer, LR= Lactate Ringer

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Start IV fluid 3ml/kg/h crystalloid solutions over 1 – 3h

No improvement, stationary (2)

Continue with the same IV Continue with the same IV fluid for another 1 – 3hfluid for another 1 – 3h

Reevaluation VS hourly

Improvement (1)

IV fluid 3 ml/kg/h another 3h

Further Improvement

IV fluid therapy for DHF grade I & II

Improvement aggravation (3)

Reevaluation Ht, VS hourly

↓IV fluid to 1.5 ml/kg/h over 3h

Still improvement

IV fluid 1.5 ml/kg/h over 24 – 48h and stop

IV fluid to 6 ml/kg/h 1 – 3h

More aggravation (4)

See DHF grade III or IV

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1. Improvement:↓ Ht, stable pulse & Blood Pressure, ↑ urine diuresis

2. No improvement, stationary:Pulse and BP not changed and still having oliguria

3. Aggravation: pulse faster and oliguria

4. More aggravation: weak and rapid pulse or not detectable, narrow pulse pressure, hypotension or not measurable blood pressure

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MENAGEMENT OF DHF Grade I and II

• Convalescent phase:

– .jaMcMNIGaharFmµta– .mintMrUveGayeRbIfñaMeLIy

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MANAGEMENT OF DHF GRADE III

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• Crystalloid solutions:- 5%D/NSS- 5%DLR*- 5%D/AR

• Colloid solution: - Dextran 40- Fresh whole blood (FWB)

Type of solutions

* * Lactate Ringer solutions are contra-indicated Lactate Ringer solutions are contra-indicated in case of acidosis.in case of acidosis. NSS or Acetate Ringer should be used instead of LR NSS or Acetate Ringer should be used instead of LR in case of shockin case of shock

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Ht immediately, IV fluid 10ml/kg/h crystalloid solutions over 1 – 2h + oxygen

No improvementImprovement

↓ IV to 6 ml/kg/h over 3h

Further Improvement

IV fluid therapy for DHF grade III

Ht

↓IV to 3 ml/kg/h over 6h

Always improvement

↓IV to 1.5 ml/kg/h over 24 –

48h and stop

Control Ht

Ht

Dextran 40 10ml/kg/h and repeated if

necessary (not exceed 30ml/kg/day)

FWB 10ml/kg/h

Improvement

↓ IV fluid of crystalloid from 10 → 6 → 3 → 1.5 ml/kg/h

No improvement

ASCB* see complications

guideline

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• A – Acidosis (Bicarbonate Na 8.4%

1ml/kg/dose)

• S – Blood sugar (<60mg%) →

D10% 5ml/kg/dose.

• C – Calcemia ( Ca gluconate 10%

1ml/kg/dose Max: 1 ampoule

• B - Bleeding → Blood Transfusion, Platelet Transfusion

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• If shock: oxygen (nasal prongs)

- Infant < 1 year = 1L/min

- Children > 1 year = 2L/min

OXYGEN USED IN SHOCK CASES

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MANAGEMENT OF DHF GRADE IV

(PROFOUND SHOCK)

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• Crystalloid solutions:

- NSS

- AR

• Colloid solution: - Dextran 40

- Fresh Whole Blood

Type of solutions

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IV fluid therapy for DHF grade IV

NSS or AR 10ml/kg bolus

Improvement No improvement

NSS/AR 10ml/kg bolus5%NSS/DAR 10ml/kg 1 – 2h

Improvement No improvementNo improvementImprovement

Lab: Hct, blood gas, ionogram, Ca, LFT, BUN, creatinin, glucose

Hct ↑ Hct ↓

FWB 10ml/kg/hDextran 40 10ml/kg/h and repeated if necessary

Improvement

↓ IV 10 → 6 → 3 → 1.5 ml/kg/h discontinue IV after 24 – 48h

No improvementImprovement

ASCB and see complications guideline

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Follow up

• .tamdan: Vital sign (CIBcr- sMBaFQam- cgVak;degðIm- kMedA), capillary refill time nig SpO2

erógral; 15-30 min.

• Urine hourly

• Consciousness hourly

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Fluid Overload• The common causes:

– Early IV fluid therapy in the early febrile phase– Use of hypotonic solution– Do not reduce the rate of IV fluid and do not

discontinue IV fluid when entering convalescence period

– Do not use colloidal solution when indicates– Do not give blood transfusion when there is

concealed bleeding and continue giving crystaloid and colloidal solutions

– Do not calculate the amount of IV fluid according to ideal body weight in obese/overweight patients

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Note for Overweight Patients

• Use ideal body weight (weight for age) to calculate the IV fluid in overweight/obese patients

• Maximum weight for IV calculation is 50 kg (for adult and overweight patients)

Weight (kg) = 2 (Age + 4)

(Child aged between 1-10 years)

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Signs of Fluid overload • .ehImRtbkEPñk• .CIBcrvayxøaMg• Dyspnea (cgVak;degðImjab;)

• Crepitation enAelIsYtTaMgsgxag• .TMhMeføImeLIgFM

(Hepatomegaly)• Turgescence of jugular veins• CXR follow the heart size: increase the heart size

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Management of Patient with Fluid Overload

• Change IV fluid to Dextran 40

• Insert urinary catheter with special precaution

• Furosemide 1mg/kg/dose IV. Vital signs should be monitored every 15 min for at least 1 hour after furosemide and observe clinical signs of shock

• Shock: Colloidal solution: Dextran 40 10ml/kg/h IV over 10-15 minutes or until the patient has stable vital signs, usually not more than 30 min and then switch to crystalloid solution.

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kMrwtFmµtaén cgVak;degðIm nig

cgVak;ebHdUg eTAtamGayu

• .Gayu cgVak;degðIm

cgVak;ebHdUg • (qñaM ) (kñúg 1 naTI)

(kñúg 1 naTI)• < 1 30-40 110-160• 2 – 5 20-30 95-140• 5 – 12 15-20 80-120• > 12 12-15 60-100

Minimum BP = 70 + (Age in year x 2)

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Criteria sMrab;eGayGñkCMgW

ecjeTApÞH• .KµanRKunekþAy:agtic 24

em:agedayKµankareRbIfñaMbBa©úHkMedAeT .

• .GñkCMgWcab;epþImXøanGahareLIgvij• Visible clinical improvement

• .GñkCMgWmanenameRcIn• Stable haematocrit

• .qøgputy:agtic 2 éf¶eRkayBI recovery from shock

• .Kµan respiratory distress EdlbNþalmkBI pleural effusion or ascites

• Platelet count elIsBI 50.000/mm3

• No other complications

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THANK YOU